Mechanisms of Mitochondrial Iron-Sulfur Protein Biogenesis.

Mitochondria are essential in most eukaryotes and are involved in numerous biological functions including ATP production, cofactor biosyntheses, apoptosis, lipid synthesis, and steroid metabolism. Work over the past two decades has uncovered the biogenesis of cellular iron-sulfur (Fe/S) proteins as the essential and minimal function of mitochondria. This process is catalyzed by the bacteria-derived iron-sulfur cluster assembly (ISC) machinery and has been dissected into three major steps: de novo synthesis of a [2Fe-2S] cluster on a scaffold protein; Hsp70 chaperone-mediated trafficking of the cluster and insertion into [2Fe-2S] target apoproteins; and catalytic conversion of the [2Fe-2S] into a [4Fe-4S] cluster and subsequent insertion into recipient apoproteins. ISC components of the first two steps are also required for biogenesis of numerous essential cytosolic and nuclear Fe/S proteins, explaining the essentiality of mitochondria. This review summarizes the molecular mechanisms underlying the ISC protein-mediated maturation of mitochondrial Fe/S proteins and the importance for human disease.

A Rich Man, Poor Man Story of S-Adenosylmethionine and Cobalamin Revisited.

S-adenosylmethionine (AdoMet) has been referred to as both "a poor man's adenosylcobalamin (AdoCbl)" and "a rich man's AdoCbl," but today, with the ever-increasing number of functions attributed to each cofactor, both appear equally rich and surprising. The recent characterization of an organometallic species in an AdoMet radical enzyme suggests that the line that differentiates them in nature will be constantly challenged. Here, we compare and contrast AdoMet and cobalamin (Cbl) and consider why Cbl-dependent AdoMet radical enzymes require two cofactors that are so similar in their reactivity. We further carry out structural comparisons employing the recently determined crystal structure of oxetanocin-A biosynthetic enzyme OxsB, the first three-dimensional structural data on a Cbl-dependent AdoMet radical enzyme. We find that the structural motifs responsible for housing the AdoMet radical machinery are largely conserved, whereas the motifs responsible for binding additional cofactors are much more varied.

METTL17 is an Fe-S cluster checkpoint for mitochondrial translation.

Friedreich's ataxia (FA) is a debilitating, multisystemic disease caused by the depletion of frataxin (FXN), a mitochondrial iron-sulfur (Fe-S) cluster biogenesis factor. To understand the cellular pathogenesis of FA, we performed quantitative proteomics in FXN-deficient human cells. Nearly every annotated Fe-S cluster-containing protein was depleted, indicating that as a rule, cluster binding confers stability to Fe-S proteins. We also observed depletion of a small mitoribosomal assembly factor METTL17 and evidence of impaired mitochondrial translation. Using comparative sequence analysis, mutagenesis, biochemistry, and cryoelectron microscopy, we show that METTL17 binds to the mitoribosomal small subunit during late assembly and harbors a previously unrecognized [Fe4S4]2+ cluster required for its stability. METTL17 overexpression rescued the mitochondrial translation and bioenergetic defects, but not the cellular growth, of FXN-depleted cells. These findings suggest that METTL17 acts as an Fe-S cluster checkpoint, promoting translation of Fe-S cluster-rich oxidative phosphorylation (OXPHOS) proteins only when Fe-S cofactors are replete.

Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes.

Oxygen is toxic across all three domains of life. Yet, the underlying molecular mechanisms remain largely unknown. Here, we systematically investigate the major cellular pathways affected by excess molecular oxygen. We find that hyperoxia destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, resulting in impaired diphthamide synthesis, purine metabolism, nucleotide excision repair, and electron transport chain (ETC) function. Our findings translate to primary human lung cells and a mouse model of pulmonary oxygen toxicity. We demonstrate that the ETC is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional ISC-containing pathways. In support of this model, primary ETC dysfunction in the Ndufs4 KO mouse model causes lung tissue hyperoxia and dramatically increases sensitivity to hyperoxia-mediated ISC damage. This work has important implications for hyperoxia pathologies, including bronchopulmonary dysplasia, ischemia-reperfusion injury, aging, and mitochondrial disorders.

The structure of the SufS-SufE complex reveals interactions driving protected persulfide transfer in iron-sulfur cluster biogenesis.

Fe-S clusters are critical cofactors for redox chemistry in all organisms. The cysteine desulfurase, SufS, provides sulfur in the SUF Fe-S cluster bioassembly pathway. SufS is a dimeric, pyridoxal 5'-phosphate-dependent enzyme that uses cysteine as a substrate to generate alanine and a covalent persulfide on an active site cysteine residue. SufS enzymes are activated by an accessory transpersulfurase protein, either SufE or SufU depending on the organism, which accepts the persulfide product and delivers it to downstream partners for Fe-S assembly. Here, using Escherichia coli proteins, we present the first X-ray crystal structure of a SufS/SufE complex. There is a 1:1 stoichiometry with each monomeric unit of the EcSufS dimer bound to one EcSufE subunit, though one EcSufE is rotated ∼7° closer to the EcSufS active site. EcSufE makes clear interactions with the α16 helix of EcSufS and site-directed mutants of several α16 residues were deficient in EcSufE binding. Analysis of the EcSufE structure showed a loss of electron density at the EcSufS/EcSufE interface for a flexible loop containing the highly conserved residue R119. An R119A EcSufE variant binds EcSufS but is not active in cysteine desulfurase assays and fails to support Fe-S cluster bioassembly in vivo. 35S-transfer assays suggest that R119A EcSufE can receive a persulfide, suggesting the residue may function in a release mechanism. The structure of the EcSufS/EcSufE complex allows for comparison with other cysteine desulfurases to understand mechanisms of protected persulfide transfer across protein interfaces.

Escherichia coli monothiol glutaredoxin GrxD replenishes Fe-S clusters to the essential ErpA A-type carrier under low iron stress.

Iron-sulfur (Fe-S) clusters are required for essential biological pathways, including respiration and isoprenoid biosynthesis. Complex Fe-S cluster biogenesis systems have evolved to maintain an adequate supply of this critical protein cofactor. In Escherichia coli, two Fe-S biosynthetic systems, the "housekeeping" Isc and "stress responsive" Suf pathways, interface with a network of cluster trafficking proteins, such as ErpA, IscA, SufA, and NfuA. GrxD, a Fe-S cluster-binding monothiol glutaredoxin, also participates in Fe-S protein biogenesis in both prokaryotes and eukaryotes. Previous studies in E. coli showed that the ΔgrxD mutation causes sensitivity to iron depletion, spotlighting a critical role for GrxD under conditions that disrupt Fe-S homeostasis. Here, we utilized a global chemoproteomic mass spectrometry approach to analyze the contribution of GrxD to the Fe-S proteome. Our results demonstrate that (1) GrxD is required for biogenesis of a specific subset of Fe-S proteins under iron-depleted conditions, (2) GrxD is required for cluster delivery to ErpA under iron limitation, (3) GrxD is functionally distinct from other Fe-S trafficking proteins, and (4) GrxD Fe-S cluster binding is responsive to iron limitation. All these results lead to the proposal that GrxD is required to maintain Fe-S cluster delivery to the essential trafficking protein ErpA during iron limitation conditions.

The ß-latch structural element of the SufS cysteine desulfurase mediates active site accessibility and SufE transpersulfurase positioning.

Under oxidative stress and iron starvation conditions, Escherichia coli uses the Suf pathway to assemble iron-sulfur clusters. The Suf pathway mobilizes sulfur via SufS, a type II cysteine desulfurase. SufS is a pyridoxal-5'-phosphate-dependent enzyme that uses cysteine to generate alanine and an active-site persulfide (C364-S-S-). The SufS persulfide is protected from external oxidants/reductants and requires the transpersulfurase, SufE, to accept the persulfide to complete the SufS catalytic cycle. Recent reports on SufS identified a conserved "ß-latch" structural element that includes the α6 helix, a glycine-rich loop, a ß-hairpin, and a cis-proline residue. To identify a functional role for the ß-latch, we used site-directed mutagenesis to obtain the N99D and N99A SufS variants. N99 is a conserved residue that connects the α6 helix to the backbone of the glycine-rich loop via hydrogen bonds. Our x-ray crystal structures for N99A and N99D SufS show a distorted beta-hairpin and glycine-rich loop, respectively, along with changes in the dimer geometry. The structural disruption of the N99 variants allowed the external reductant TCEP to react with the active-site C364-persulfide intermediate to complete the SufS catalytic cycle in the absence of SufE. The substitutions also appear to disrupt formation of a high-affinity, close approach SufS-SufE complex as measured with fluorescence polarization. Collectively, these findings demonstrate that the ß-latch does not affect the chemistry of persulfide formation but does protect it from undesired reductants. The data also indicate the ß-latch plays an unexpected role in forming a close approach SufS-SufE complex to promote persulfide transfer.

Efficient NADPH-dependent dehalogenation afforded by a self-sufficient reductive dehalogenase.

Reductive dehalogenases are corrinoid and iron-sulfur cluster-containing enzymes that catalyze the reductive removal of a halogen atom. The oxygen-sensitive and membrane-associated nature of the respiratory reductive dehalogenases has hindered their detailed kinetic study. In contrast, the evolutionarily related catabolic reductive dehalogenases are oxygen tolerant, with those that are naturally fused to a reductase domain with similarity to phthalate dioxygenase presenting attractive targets for further study. We present efficient heterologous expression of a self-sufficient catabolic reductive dehalogenase from Jhaorihella thermophila in Escherichia coli. Combining the use of maltose-binding protein as a solubility-enhancing tag with the btuCEDFB cobalamin uptake system affords up to 40% cobalamin occupancy and a full complement of iron-sulfur clusters. The enzyme is able to efficiently perform NADPH-dependent dehalogenation of brominated and iodinated phenolic compounds, including the flame retardant tetrabromobisphenol, under both anaerobic and aerobic conditions. NADPH consumption is tightly coupled to product formation. Surprisingly, corresponding chlorinated compounds only act as competitive inhibitors. Electron paramagnetic resonance spectroscopy reveals loss of the Co(II) signal observed in the resting state of the enzyme under steady-state conditions, suggesting accumulation of Co(I)/(III) species prior to the rate-limiting step. In vivo reductive debromination activity is readily observed, and when the enzyme is expressed in E. coli strain W, supports growth on 3-bromo-4-hydroxyphenylacetic as a sole carbon source. This demonstrates the potential for catabolic reductive dehalogenases for future application in bioremediation.

FDX1 regulates cellular protein lipoylation through direct binding to LIAS.

Ferredoxins are a family of iron-sulfur (Fe-S) cluster proteins that serve as essential electron donors in numerous cellular processes that are conserved through evolution. The promiscuous nature of ferredoxins as electron donors enables them to participate in many metabolic processes including steroid, heme, vitamin D, and Fe-S cluster biosynthesis in different organisms. However, the unique natural function(s) of each of the two human ferredoxins (FDX1 and FDX2) are still poorly characterized. We recently reported that FDX1 is both a crucial regulator of copper ionophore-induced cell death and serves as an upstream regulator of cellular protein lipoylation, a mitochondrial lipid-based post-translational modification naturally occurring on four mitochondrial enzymes that are crucial for TCA cycle function. Here we show that FDX1 directly regulates protein lipoylation by binding the lipoyl synthase (LIAS) enzyme promoting its functional binding to the lipoyl carrier protein GCSH and not through indirect regulation of cellular Fe-S cluster biosynthesis. Metabolite profiling revealed that the predominant cellular metabolic outcome of FDX1 loss of function is manifested through the regulation of the four lipoylation-dependent enzymes ultimately resulting in loss of cellular respiration and sensitivity to mild glucose starvation. Transcriptional profiling established that FDX1 loss-of-function results in the induction of both compensatory metabolism-related genes and the integrated stress response, consistent with our findings that FDX1 loss-of-function is conditionally lethal. Together, our findings establish that FDX1 directly engages with LIAS, promoting its role in cellular protein lipoylation, a process essential in maintaining cell viability under low glucose conditions.

Ferredoxins: Functions, Evolution, Potential Applications, and Challenges of Subtype Classification.

Ferredoxins are proteins found in all biological kingdoms and are involved in essential biological processes including photosynthesis, lipid metabolism, and biogeochemical cycles. Ferredoxins are classified into different groups based on the iron-sulfur (Fe-S) clusters that they contain. A new subtype classification and nomenclature system, based on the spacing between amino acids in the Fe-S binding motif, has been proposed in order to better understand ferredoxins' biological diversity and evolutionary linkage across different organisms. This new classification system has revealed an unparalleled diversity between ferredoxins and has helped identify evolutionarily linked ferredoxins between species. The current review provides the latest insights into ferredoxin functions and evolution, and the new subtype classification, outlining their potential biotechnological applications and the future challenges in streamlining the process.

In Situ Fast Construction of Ni3S4/FeS Catalysts on 3D Foam Structure Achieving Stable Large-Current-Density Water Oxidation.

By increasing the content of Ni3+, the catalytic activity of nickel-based catalysts for the oxygen evolution reaction (OER), which is still problematic with current synthesis routes, can be increased. Herein, a Ni3+-rich of Ni3S4/FeS on FeNi Foam (Ni3S4/FeS@FNF) via anodic electrodeposition to direct obtain high valence metal ions for OER catalyst is presented. XPS showed that the introduction of Fe not only further increased the Ni3+ concentration in Ni3S4/FeS to 95.02%, but also inhibited the dissolution of NiOOH by up to seven times. Furthermore, the OER kinetics is enhanced by the combination of the inner Ni3S4/FeS heterostructures and the electrochemically induced surface layers of oxides/hydroxides. Ni3S4/FeS@FNF shows the most excellent OER activity with a low Tafel slope of 11.2 mV dec-1 and overpotentials of 196 and 445 mV at current densities of 10 and 1400 mA cm-2, respectively. Furthermore, the Ni3S4/FeS@FNF catalyst can be operated stably at 1500 mA cm-2 for 200 h without significant performance degradation. In conclusion, this work has significantly increased the high activity Ni3+ content in nickel-based OER electrocatalysts through an anodic electrodeposition strategy. The preparation process is time-saving and mature, which is expected to be applied in large-scale industrialization.

Synthesis of Ultrathin FeS Nanosheets via Chemical Vapor Deposition.

Fe-based 2D materials exhibit rich chemical compositions and structures, which may imply many unique physical properties and promising applications. However, achieving controllable preparation of ultrathin non-layered FeS crystal on SiO2/Si substrate remains a challenge. Herein, the influence of temperature and molecular sieves is reported on the synthesis of ultrathin FeS nanosheets with a thickness as low as 2.3 nm by molecular sieves-assisted chemical vapor deposition (CVD). The grown FeS nanosheets exhibit a non-layered hexagonal NiAs structure and belong to the P63/mmc space group. The inverted symmetry broken structure is confirmed by the angle-resolved second harmonic generation (SHG) test. In particular, the 2D FeS nanosheets exhibit exceptional metallic behavior, with conductivity up to 1.63 × 106 S m-1 at 300 K for an 8 nm thick sample, which is higher than that of reported 2D metallic materials. This work provides a significant contribution to the synthesis and characterization of 2D non-layered Fe-based materials.

Suppressing Surface Oxidation of Pyrite FeS2 by Cobalt Doping in Lithium Sulfur Batteries.

Lithium-sulfur batteries have emerged as a promising energy storage device due to ultra-high theoretical capacity, but the slow kinetics of sulfur and polysulfide shuttle hinder the batteries' further development. Here, the 10% cobalt-doped pyrite iron disulfide electrocatalyst deposited on acetylene black as a separator coating in lithium-sulfur batteries is reported. The adsorption rate to the intermediate Li2S6 is significantly improved while surface oxidation of FeS2 is inhibited: iron oxide and sulfate, thus avoiding FeS2 electrocatalyst deactivation. The electrocatalytic activity has been evaluated in terms of electronic resistivity, lithium-ion diffusion, liquid-liquid, and liquid-solid conversion kinetics. The coin batteries exhibit ultra-long cycle life at 1 C with an initial capacity of 854.7 mAh g-1 and maintained at 440.8 mAh g-1 after 920 cycles. Furthermore, the separator is applied to a laminated pouch battery with a sulfur mass of 326 mg (3.7 mg cm-2) and retained the capacity of 590 mAh g-1 at 0.1 C after 50 cycles. This work demonstrates that FeS2 electrocatalytic activity can be improved when Co-doped FeS2 suppresses surface oxidation and provides a reference for low-cost separator coating design in pouch batteries.

S@FeS2 Core-Shell Cathode Nanomaterial for Preventing Polysulfides Shuttling and Forming Solid Electrolyte Interphase in High-Rate Li-S Batteries.

Lithium-sulfur (Li-S) battery is a potential next-generation energy storage technology over lithium-ion batteries for high capacity, cost-effective, and environmentally friendly solutions. However, several issues including polysulfides shuttle, low conductivity and limited rate-capability have hampered its practical application. Herein, a new class of cathode active material with perfect core-shell structure is reported, in which sulfur is fully encapsulated by conductivity-enhancing FeS2 (named as S@FeS2), for high-rate application. Surface-stabilized S@FeS2 cathode exhibits a stable cycling performance under 2 - 20 times higher rates (1-2 C, charged in 30-60 min) than standard rates (e.g., 0.1-0.5 C, charged in 2-10 h), without polysulfides shuttle event. Surface analysis results reveal the unprecedented formation of a stable solid electrolyte interphase (SEI) layer on S@FeS2 cathode, which is distinguished from other sulfur-based cathodes that are not able to form the SEI layer. The data suggest that the prevention of polysulfides shuttling is owing to the surface protection effect of FeS2 shell and the SEI layer formation overlying core-shell S@FeS2. This unique and potential material concept proposed in the present study will give insight into designing a prospective fast charging Li-S battery.

EPR studies of ferredoxin in spinach and cyanobacterial thylakoids related to photosystem I-driven NADP+ reduction.

Photosynthetic light-dependent reactions occur in thylakoid membranes where embedded proteins capture light energy and convert it to chemical energy in the form of ATP and NADPH for use in carbon fixation. One of these integral membrane proteins is Photosystem I (PSI). PSI catalyzes light-driven transmembrane electron transfer from plastocyanin (Pc) to oxidized ferredoxin (Fd). Electrons from reduced Fd are used by the enzyme ferredoxin-NADP+ reductase (FNR) for the reduction of NADP+ to NADPH. Fd and Pc are both small soluble proteins whereas the larger FNR enzyme is associated with the membrane. To investigate electron shuttling between these diffusible and embedded proteins, thylakoid photoreduction of NADP+ was studied. As isolated, both spinach and cyanobacterial thylakoids generate NADPH upon illumination without extraneous addition of Fd. These findings indicate that isolated thylakoids either (i) retain a "pool" of Fd which diffuses between PSI and membrane bound FNR or (ii) that a fraction of PSI is associated with Fd, with the membrane environment facilitating PSI-Fd-FNR interactions which enable multiple turnovers of the complex with a single Fd. To explore the functional association of Fd with PSI in thylakoids, electron paramagnetic resonance (EPR) spectroscopic methodologies were developed to distinguish the signals for the reduced Fe-S clusters of PSI and Fd. Temperature-dependent EPR studies show that the EPR signals of the terminal [4Fe-4S] cluster of PSI can be distinguished from the [2Fe-2S] cluster of Fd at > 30 K. At 50 K, the cw X-band EPR spectra of cyanobacterial and spinach thylakoids reduced with dithionite exhibit EPR signals of a [2Fe-2S] cluster with g-values gx = 2.05, gy = 1.96, and gz = 1.89, confirming that Fd is present in thylakoid preparations capable of NADP+ photoreduction. Quantitation of the EPR signals of P700+ and dithionite reduced Fd reveal that Fd is present at a ratio of ~ 1 Fd per PSI monomer in both spinach and cyanobacterial thylakoids. Light-driven electron transfer from PSI to Fd in thylakoids confirms Fd is functionally associated (< 0.4 Fd/PSI) with the acceptor end of PSI in isolated cyanobacterial thylakoids. These EPR experiments provide a benchmark for future spectroscopic characterization of Fd interactions involved in multistep relay of electrons following PSI charge separation in the context of photosynthetic thylakoid microenvironments.

Exploring the novel duo of Reticulocalbin, and Sideroflexin as future biomarker candidates for Exacerbated Chronic Obstructive Pulmonary Disease.

BACKGROUND: COPD is a complex respiratory disorder with high morbidity and mortality rates. Even with the current conventional diagnostic methods, including circulating inflammatory biomarkers, underdiagnosis rates in COPD remain as high as 70%. Our study was a comparative cross-sectional study that aimed to address the diagnostic challenges by identifying future biomarker candidates in COPD variants. METHODS: This study used a label-free plasma proteomics approach that combined mass spectrometric data with bioinformatics to shed light on the functional roles of differentially expressed proteins in the COPD lung microenvironment. The predictive capacity of the screened proteins was assessed using Receiver Operating Characteristic (ROC) curves, with Western blot analysis validating protein expression patterns in an independent cohort. RESULTS: Our study identified three DEPs-reticulocalbin-1, sideroflexin-4, and liprinα-3 that consistently exhibited altered expression in COPD exacerbation. ROC analysis indicated strong predictive potential, with AUC values of 0.908, 0.715, and 0.856 for RCN1, SFXN4, and LIPα-3, respectively. Validation through Western blot analysis confirmed their expression patterns in an independent validation cohort. CONCLUSIONS: Our study discovered a novel duo of proteins reticulocalbin-1, and sideroflexin-4 that showed potential as valuable future biomarkers for the diagnosis and clinical management of COPD exacerbations.

The FES Gene at the 15q26 Coronary-Artery-Disease Locus Inhibits Atherosclerosis.

BACKGROUND: Genome-wide association studies have discovered a link between genetic variants on human chromosome 15q26.1 and increased coronary artery disease (CAD) susceptibility; however, the underlying pathobiological mechanism is unclear. This genetic locus contains the FES (FES proto-oncogene, tyrosine kinase) gene encoding a cytoplasmic protein-tyrosine kinase involved in the regulation of cell behavior. We investigated the effect of the 15q26.1 variants on FES expression and whether FES plays a role in atherosclerosis. METHODS AND RESULTS: Analyses of isogenic monocytic cell lines generated by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that monocytes with an engineered 15q26.1 CAD risk genotype had reduced FES expression. Small-interfering-RNA-mediated knockdown of FES promoted migration of monocytes and vascular smooth muscle cells. A phosphoproteomics analysis showed that FES knockdown altered phosphorylation of a number of proteins known to regulate cell migration. Single-cell RNA-sequencing revealed that in human atherosclerotic plaques, cells that expressed FES were predominately monocytes/macrophages, although several other cell types including smooth muscle cells also expressed FES. There was an association between the 15q26.1 CAD risk genotype and greater numbers of monocytes/macrophage in human atherosclerotic plaques. An animal model study demonstrated that Fes knockout increased atherosclerotic plaque size and within-plaque content of monocytes/macrophages and smooth muscle cells, in apolipoprotein E-deficient mice fed a high fat diet. CONCLUSIONS: We provide substantial evidence that the CAD risk variants at the 15q26.1 locus reduce FES expression in monocytes and that FES depletion results in larger atherosclerotic plaques with more monocytes/macrophages and smooth muscle cells. This study is the first demonstration that FES plays a protective role against atherosclerosis and suggests that enhancing FES activity could be a potentially novel therapeutic approach for CAD intervention.

18F-Labeled Fluoroestradiol PET/CT: Current Status, Gaps in Knowledge, and Controversies-AJR Expert Panel Narrative Review.

PET/CT using 16α-[18F]-fluoro-17ß-estradiol (FES) noninvasively images tissues expressing estrogen receptors (ERs). FES has undergone extensive clinicopathologic validation for ER-positive breast cancer and in 2020 received FDA approval for clinical use as an adjunct to biopsy in patients with recurrent or metastatic ER-positive breast cancer. Clinical use of FES PET/CT is increasing but is not widespread in the United States. This AJR Expert Panel Narrative Review explores the present status and future directions of FES PET/CT, including image interpretation, existing and emerging uses, knowledge gaps, and current controversies. Specific controversies discussed include whether both FES PET/CT and FDG PET/CT are warranted in certain scenarios, whether further workup is required after negative FES PET/CT results, whether FES PET/CT findings should inform endocrine therapy selection, and whether immunohistochemistry should remain the stand-alone reference standard for determining ER status for all breast cancers. Consensus opinions from the panel include agreement with the appropriate clinical uses of FES PET/CT published by a multidisciplinary expert work group in 2023, anticipated expanded clinical use of FES PET/CT for staging ER-positive invasive lobular carcinomas and low-grade invasive ductal carcinomas pending ongoing clinical trial results, and the need for further research regarding the use of FES PET/CT for nonbreast malignancies expressing ER.

Phosphate-Induced Acidic Microenvironment for Improved Contaminant Removal during FeS Oxygenation.

The coexistence of mackinawite (FeS) and phosphate is widely observed in natural systems. However, the underlying mechanism regarding how phosphate influences the environmental behavior of FeS, especially during the FeS oxygenation in aquatic systems, remains in its fancy. This study for the first time reported that the presence of phosphate, even at a low concentration of 0.3 mM, significantly promoted the FeS-mediated O2 activation and thus the pollutant degradation. The enhancement was attributed to a substantial increase in the generation of •OH, as evidenced by the electron paramagnetic resonance tests and the identification of the probing products. A combination of experiments and theoretical calculations revealed that phosphate adsorbed onto the FeS surface via a monodentate mononuclear configuration, establishing an acidic microenvironment on the FeS surface. Such acidic microenvironment not only increased the utilization efficiency of Fe(II) toward H2O2 generation (i.e., O2+2H++2Fe(II)→H2O2+2Fe(III)), but also prevented the subsequent side reaction of H2O2 self-decomposition (i.e., H2O2+OH-→HO2-+H2O). The results highlight the beneficial role of commonly encountered phosphate in FeS-based systems, which has profound implications for the degradation of waterborne contaminants.

Cr(VI) Reduction and Sequestration by FeS Nanoparticles Formed in situ as Aquifer Material Coating to Create a Regenerable Reactive Zone.

Remediation of large and dilute plumes of groundwater contaminated by oxidized pollutants such as chromate is a common and difficult challenge. Herein, we show that in situ formation of FeS nanoparticles (using dissolved Fe(II), S(-II), and natural organic matter as a nucleating template) results in uniform coating of aquifer material to create a regenerable reactive zone that mitigates Cr(VI) migration. Flow-through columns packed with quartz sand are amended first with an Fe2+ solution and then with a HS- solution to form a nano-FeS coating on the sand, which does not hinder permeability. This nano-FeS coating effectively reduces and immobilizes Cr(VI), forming Fe(III)-Cr(III) coprecipitates with negligible detachment from the sand grains. Preconditioning the sand with humic or fulvic acid (used as model natural organic matter (NOM)) further enhances Cr(VI) sequestration, as NOM provides additional binding sites of Fe2+ and mediates both nucleation and growth of FeS nanoparticles, as verified with spectroscopic and microscopic evidence. Reactivity can be easily replenished by repeating the procedures used to form the reactive coating. These findings demonstrate that such enhancement of attenuation capacity can be an effective option to mitigate Cr(VI) plume migration and exposure, particularly when tackling contaminant rebound post source remediation.